Investigation of Drug Nanoparticle Formation by Co-grinding with Cyclodextrins: Studies for Indomethacin, Furosemide and Naproxen
27
Citation
10
Reference
10
Related Paper
Citation Trend
Keywords:
Naproxen Sodium
Nap
Fraction (chemistry)
To compare efficacy and gastrointestinal (GI) tolerability of a new enteric coated formulation of naproxen (NAP-EC) with standard immediate release naproxen (NAP-STD).One hundred seventy-nine patients with osteoarthritis (OA) and one hundred seventy-six patients with rheumatoid arthritis (RA) at high risk for developing GI side effects to nonsteroidal antiinflammatory drug (NSAID) therapy were enrolled in a double blind, parallel, multicenter study. All patients had either discontinued as NSAID during the previous one year or required cotreatment with antiulcer drugs for control of GI complaints related to NSAID use. The treatments were evenly divided in both diagnostic cohorts.Except for minor differences in alcohol consumption, baseline characteristics of patients in both treatment groups were statistically similar. Both naproxen formulations were highly efficacious by all variables of disease activity when changes were measured from baseline. No statistically significant between formulation difference was found in the primary efficacy variable, overall disease activity. Overall, between formulation differences in efficacy measures were few, though most favored NAP-STD. GI complaints were reduced by 15% (51% NAP-EC vs 60% NAP-STD, p = 0.077) and GI complaints thought to be drug related were reduced by 36% (16% NAP-EC vs 25% NAP-STD, p = 0.024). Withdrawals due to GI complaints were reduced by 37% in the NAP-EC group (12% NAP-EC vs 19% NAP-STD, p = 0.054), and withdrawals due to GI complaints judged to be drug related were reduced by 55% in the NAP-EC group (6% NAP-EC vs 12% NAP-STD, p = 0.025).Enteric coated naproxen is an effective treatment for OA and RA. All observed differences in GI tolerability favor NAP-EC over NAP-STD.
Nap
Tolerability
Cite
Citations (12)
Naproxen Sodium
Cite
Citations (0)
As the trend for Americans to self-medicate continues to increase, it becomes important to review the safety of over-the-counter (OTC) medications. This article will review the safety of an OTC analgesic, Aleve (naproxen sodium). The objective of this meta-analysis is to evaluate the frequency of occurrence of all adverse events in subjects taking various doses of OTC naproxen sodium as compared to placebo. These varying doses and dosage regimens were studied individually and consisted of 220 to 880 mg administered in single, multiple, and PRN (as needed) doses of naproxen sodium. This meta-analysis confirmed the favorable safety profile of naproxen sodium at OTC doses and established that the overall occurrence of adverse events with naproxen sodium was comparable and in some cases significantly lower than placebo. These results indicate that treatment with naproxen sodium may be highly beneficial from a clinical and economical perspective and safe when adhering to labeled directions.
Naproxen Sodium
Over-the-counter
Cite
Citations (32)
The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26-7, Aprenin, test drug), and the sodium salt of S-naproxen (reference), were administered to twelve healthy volunteers of both sexes according to a crossover design, in a single dose of one 575 mg capsule of test, containing 342 mg of S-naproxen and two 275 mg tablets of reference, containing 502 mg of S-naproxen. Blood samples were drawn off over a 24-h period before (time 0) and after administration at foreseen time intervals. Naproxen was measured in plasma by a validated HPLC assay with UV detection which was able to detect 1 microgram/ml and proved to be linear in the range 1-100 micrograms/ml. The non-compartmental pharmacokinetic parameters obtained were statistically processed according to the EU guidance note on bioavailability and bioequivalence Cmax, AUC0-24h and AUC0-infinity were normalized to the dose of 502 mg of naproxen and log-transformed before statistical analysis to assess bioequivalence. Dose-normalized values of plasma concentrations encountered with the two formulations proved to overlap, with the exception of the first sampling time which showed naproxen concentrations that were higher with test drug than with reference. The specific test for bioequivalence led to 90% confidence intervals within the 80-125% range with target pharmacokinetic parameters, whereas the time to peak (tmax) observed with the test and reference drugs did not differ to any statistically significant degree when analysed with Wilcoxon's non-parametric test. It is concluded that the test drug should be declared bioequivalent with the reference drug in terms of dose-normalized concentrations, despite the more rapid increase in plasma concentrations of naproxen observed at the first sampling time with test drug.
Bioequivalence
Naproxen Sodium
Crossover study
Cite
Citations (5)
Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID) that suffers from limited water solubility. The inclusion complexation with cyclodextrin (CD) can eliminate this drawback and the free-standing nanofibrous film (NF) generated from these inclusion complexes (ICs) can be a promising alternative formula as an orally disintegrating drug delivery system. For this, naproxen/CD IC NFs were generated using the highly water soluble hydroxypropylated derivative of βCD (HPβCD) with two different molar ratios of 1/1 and 1/2 (drug/CD). The complexation energy calculated by the modeling study demonstrated a more favorable interaction between HPβCD and naproxen for the 1/2 molar ratio than 1/1. HPβCD/naproxen IC NFs were generated with loading concentrations of ∼7-11% and without using toxic chemicals. HPβCD/naproxen IC NFs indicated a faster and enhanced release profile in aqueous medium compared to pure naproxen owing to inclusion complexation. Moreover, rapid disintegration in less than a second was achieved in an artificial saliva environment.
Molar ratio
Inclusion compound
Naproxen Sodium
Beta-Cyclodextrins
Cite
Citations (2)
Nap
Naproxen Sodium
Ibuprofen
Acetaminophen
Cite
Citations (59)
Naproxen Sodium
Recrystallization (geology)
Cite
Citations (15)
1 In the first of a series of trials with naproxen sodium it was shown that patients achieved significantly earlier and higher plasma levels of naproxen when naproxen sodium was administered. 2 In a second study comparing naproxen with naproxen sodium in patients with post‐partum pain, pain intensity was consistently lower for the group receiving naproxen sodium. However, statistically significant differences were not seen until 4 to 5 h after medication. 3 A final study documented that a more frequent dosage schedule of every 6 h led to clearly higher plasma levels than those achieved with an every 8 h regimen; plasma levels did not plateau. Doses up to 1,375 mg/day were well tolerated. 4 In conclusion, naproxen sodium appears to be an improved form of naproxen for use as a analgesic agent.
Naproxen Sodium
Cite
Citations (103)
Bioavailability and absorption characteristics of naproxen sodium have been shown to be superior to that of naproxen in tablet formulations. In this study naproxen sodium suppositories were compared with naproxen tablets and naproxen suppositories with respect to plasma concentrations and bioavailability of naproxen. Eleven healthy volunteers participated in a randomized crossover study comparing naproxen sodium suppositories (equivalent to 500 mg naproxen) and naproxen suppositories (500 mg). Tmax (1.4 h) was significantly shorter after the administration of naproxen sodium suppositories than after naproxen tablets (2.4 h), whereas Cmax was higher after the tablet formulation. No difference was observed with respect to bioavailability and biologic half-life of naproxen. In a second crossover study in six volunteers suppositories containing either naproxen sodium or naproxen were compared. Tmax was shorter and Cmax significantly higher after administration of the sodium naproxen suppository formulation. The sodium naproxen suppositories were well tolerated and proved to be a safe and reliable way of administering naproxen, giving therapeutic naproxen concentrations within the 1st h after administration.
Naproxen Sodium
Suppository
Crossover study
Cite
Citations (10)
Extended-release (ER) naproxen sodium provides pain relief for up to 24 hours with a single dose (660 mg/day). Its pharmacokinetic profile after single and multiple dosing was compared to immediate release (IR) naproxen sodium in two randomized, open-label, crossover studies, under fasting and fed conditions.Eligible healthy subjects were randomized to ER naproxen sodium 660-mg tablet once daily or IR naproxen sodium 220-mg tablet twice daily (440 mg initially, followed by 220 mg 12 hours later). Primary variables: pharmacokinetic parameters after singleday administration (day 1) and at steady state after multiple-day administration (day 6).Total exposure was comparable for both treatments under fasting and fed conditions. After fasting: peak naproxen concentrations were slightly lower with ER naproxen sodium than with IR naproxen sodium but were reached at a similar time. Fed conditions: mean peak concentrations were comparable but reached after a longer time with ER vs. IR naproxen sodium. ER naproxen sodium was well tolerated, with a similar safety profile to IR naproxen sodium.The total exposure of ER naproxen sodium (660 mg) is comparable to IR naproxen sodium (220 mg) when administered at the maximum over the counter (OTC) dose of 660-mg daily dose on a single day and over multiple days. The rate of absorption is delayed under fed conditions.
Naproxen Sodium
Crossover study
Cite
Citations (2)